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A computational modelling study from the King Group demonstrates that the way sounds are transformed from the ear to the brain’s auditory cortex may be simpler than expected. These findings not only highlight the value of computational modelling for determining the principles underlying neural processing, but could also be useful for improving treatments for patients with hearing loss.
Neurotransmitter modulation of human facial emotion recognition
Human facial emotion recognition (FER) is an evolutionarily preserved process that influences affiliative behaviours, approach/avoidance and fight-or-flight responses in the face of detecting threat cues, thus enhancing adaptation and survival in social groups. Here, we provide a narrative literature review on how human FER is modulated by neurotransmitters and pharmacological agents, classifying the documented effects by central neurotransmitter systems. Synthesising the findings from studies involving functional neuroimaging and FER tasks, we highlight several emerging themes; for example, noradrenaline promotes an overall positive bias in FER, while serotonin, dopamine and gamma-aminobutyric acid modulate emotions relating to self-preservation. Finally, other neurotransmitters including the cholinergic and glutamatergic systems are responsible for rather non-specific pro-cognitive effects in FER. With the ongoing accumulation of evidence further characterising the individual contributions of each neurotransmitter system, we argue that a sensible next step would be the integration of experimental neuropharmacology with computational models to infer further insights into the temporal dynamics of different neurotransmitter systems modulating FER.
"The traditional healer said, 'I had a genie that scared me in my eyes, and that is why I fall": An ethnographic study in Mahenge, Tanzania.
BACKGROUND: In many low-income countries, individuals with epilepsy often turn to traditional healers as their first source of treatment after the onset of seizures. However, their experiences with traditional healing practices remain poorly understood. This study examines the perceptions and experiences of people with epilepsy in relation to traditional healing in Mahenge, Tanzania. METHODS: A culturally specific ethnographic approach, centred on oral history, was employed to capture rich, contextually grounded narratives. A total of 45 oral history interviews were conducted with individuals living with epilepsy from 21 villages in Mahenge. Participants were purposively selected based on the following criteria: being at least 18 years of age, having a diagnosis of epilepsy, and the ability to recount their experiences in Swahili, the primary language spoken in the region. Data were manually analysed using thematic analysis. RESULTS: Traditional healers often attribute epilepsy to supernatural causes, such as curses or witchcraft, linking seizure onset to past events believed to have triggered the condition. Their treatment practices are frequently accompanied by strict behavioural restrictions, which can be challenging for individuals with epilepsy to follow and are sometimes cited as reasons for treatment failure. Moreover, some participants reported experiences of physical, emotional, and even sexual harassment during their encounters with traditional healers. CONCLUSION: There is a strong reliance on traditional healing practices for epilepsy, where cultural beliefs and rituals can hinder accurate diagnosis and effective care. Raising awareness about epilepsy, its medical management, and the rights of people with epilepsy, both among traditional healers and the broader community, is essential to improve care and protect the well-being of those affected.
Knowledge, Attitudes, and Experiences of Self-Harm and Suicide in Low- and Middle-Income Countries.
Background: Over three-quarters of suicides occur in low- and middle-income countries (LMICs) and a better understanding of this behavior within these settings is crucial. Aim: To investigate stakeholders' knowledge, attitudes, and experiences of self-harm and suicide in LMICs. Method: A systematic search was conducted using British Nursing Index, Cochrane Library, Cumulative Index to Nursing and Allied Health Literature, Embase, MEDLINE, PsycINFO, and Social Sciences electronic databases from inception to March 2022, combined with hand-searching reference lists. The search was updated using the PubMed Similar Articles function in February 2024. Analysis followed a modified narrative synthesis approach. Results: One hundred and fifty-four articles met the inclusion criteria, of which 60 included relevant quantitative data. Attitudes toward suicide were often contradictory although, overall, were negative and suicide literacy was poor. Healthcare staff reported lacking training in this area. Willingness to seek help was linked to suicide literacy and attitudes toward suicide. Limitations: Heterogeneity of included studies. Conclusion: Tackling stigma and improving awareness of suicide and self-harm in LMICs are needed to facilitate suicide prevention. Training should include people with lived experience of suicide and self-harm. The complex and contradictory influences of age, gender, religious, and cultural beliefs and lived experience must be considered.
‘Not Angels but Humans’ An Exploratory Qualitative Study of Female Nurses With Lived Experience of Self-Harm and Suicidal Behaviours
Aims: To explore the experiences of qualified nurses who have lived experience of self-harm (with or without suicidal intent) during nursing training or practice. Specifically, to examine characteristics and contributing factors and ideas for tailored suicide prevention interventions. Design: Exploratory qualitative study. Methods: Individual semi-structured interviews were conducted with eight qualified female nurses who had self-harmed during nursing training or practice. Participants were recruited from three NHS hospital Trusts. Data were collected between June and September 2023 and analysed using reflexive thematic analysis. Results: Four themes were generated: (1) ‘I don't think work triggered it, but I don't think it helped’: characteristics and contributors to self-harm, (2) ‘You're a nurse now you can't talk about that’: nursing culture and barriers to workplace support seeking, (3) ‘Are you a nurse or are you a lived experience practitioner – can you be both?’: navigating a dual identity as a nurse with lived experience and (4) ‘We need the permission that it's ok to put us first’: workplace support and suggestions for suicide prevention. Conclusion: Participants described their experiences of self-harm, including citing a range of contributory factors, with occupational issues being particularly salient. Cultural expectations and stigma prevented help-seeking and unique challenges regarding being both a clinician and an individual who has self-harmed were described. Reflections and perspectives on workplace and independent mental health support for nurses were shared. Implications for the Profession: Potential avenues for suicide prevention interventions tailored for the nursing profession may include challenging nursing culture and promoting help-seeking, peer support opportunities and implementation of education surrounding mental health and well-being in nursing curricula. Reporting Method: Reporting complied with the COREQ. Patient or Public Contribution: The topic guide and participant information sheet were developed in consultation with a group of qualified and student nurses with lived experience of suicidal thoughts and behaviours.
What do people do in the aftermath of healthcare-related harm? A qualitative study on experiences and factors influencing decision-making.
OBJECTIVES: To capture experiences of people self-reporting harm and contrast responses and actions between those who do or do not take formal action. DESIGN: Semi-structured qualitative interview study. SETTING: People self-reporting harm experienced in the National Health Service (NHS) or their family/friends identified from a general Great British population survey. PARTICIPANTS: 49 participants. RESULTS: There were commonalities in experiences after harm whether formal action (including making a formal complaint or litigation) was taken or not. Many participants reported raising concerns informally with NHS staff, trying to access explanations or support, but were usually unsuccessful. Decision-making on action was complex. There were multiple reasons for not pursuing formal action, including fears of damaging relationships with clinicians, being occupied coping with the consequences of the harm or not wanting to take action against the NHS. NHS advocacy services were not regarded as helpful. Knowledge of how to proceed and feeling entitled to do so, along with proactive social networks, could facilitate action, but often only after people were spurred on by anger and frustration about not receiving an explanation, apology or support for recovery from the NHS. Those from marginalised groups were more likely to feel disempowered to act or be discouraged by family or social contacts, which could lead to self-distancing and reduced trust in services. CONCLUSIONS: People actively seek resolution and recovery after harm but often face multiple barriers in having their needs for explanations, apologies and support addressed. Open and compassionate engagement, especially with those from more marginalised communities, plus tailored support to address needs, could promote recovery, decrease compounded harm and reduce use of grievance services where other provision may be more helpful.
THE OXFORD CHARACTER PROJECT*
The Oxford Character Project (OCP) is an interdisciplinary research and education project at the University of Oxford. Established in 2014, its work joins theoretical and empirical research in virtue ethics, character development and leadership education with the design and delivery of character and leadership development programmes. Its aim is to advance character-based leadership and leadership education through strategic partnerships in the United Kingdom and around the world. This chapter presents the work of the OCP, focusing on: (1) the OCP’s approach to character education, (2) the connection between character and leadership that is manifested in several educational programmes, (3) the OCP’s research on character, culture and leadership in UK business and (4) the OCP’s research on global leadership.
Neurosurgery
The nervous system is the principal means with which we negotiate the outside world. Injury to the nervous system (brain, spinal cord and nerves) therefore may result not simply in physical impairments, but psychological, social and economic impairments too. Legal proceedings therefore may focus upon the effect of medical errors on claimants’ psychological, economic or social capacities, not simply on physical harm. The role of neurosurgery in many disorders of the nervous system concerns prevention of secondary injury: despite the sophistication of modern medicine, damage to the nervous system caused by a primary event (for example, head injury, spontaneous bleed, acutely prolapsed disc) is often irreversible and may set a spiral of deterioration in motion that may be beyond the abilities of physicians to halt.The scope of this chapter is to describe current management strategies of nervous system disorders in which a neurosurgeon would be reasonably expected to play a lead role, although not necessarily an exclusive role. Neurosurgery is a ‘tertiary service’ in the NHS, meaning a patient may have been managed by another hospital-based specialist, or even pre-hospital specialist, prior to transfer to the care of a neurosurgeon. Neurosurgeons may therefore become involved in complaints arising from problems with delayed diagnosis or timely transfer to neurosurgical care, in addition to surgical and post-surgical care.
Outcomes for older people with screening-detected versus existing chronic kidney disease: a cohort study with data linkage.
BACKGROUND: Chronic kidney disease (CKD) is a common health problem associated with increased risk of cardiovascular disease (CVD), end-stage kidney disease (ESKD), and premature death. It is estimated that one-third of people aged ≥70 years have CKD globally, many of whom are undiagnosed, but little is known about the value of screening. AIM: To compare the risk of adverse health outcomes between people with an existing diagnosis of CKD and those identified through screening, and identify factors associated with mortality in CKD. DESIGN & SETTING: Prospective cohort study of 892 primary care patients aged ≥60 years with CKD (existing and screening detected) in Oxfordshire, with data linkage to civil death registry and secondary care. METHOD: Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using Cox proportional hazard models to compare the risk of all-cause mortality, hospitalisation, CVD, ESKD separately, and as a composite between CKD groups, as well as to identify factors associated with mortality. RESULTS: After a median follow-up of 3-5 years, 49 people died, 512 were hospitalised, 78 had an incident CVD event, and none had an ESKD event. There was no difference in the composite outcome between those with existing CKD and those identified through screening (HR 0.94, 95% CI = 0.67 to 1.33). Older age (HR 1.10, 95% CI = 1.06 to 1.15), male sex (HR 2.31, 95% CI = 1.26 to 4.24), and heart failure (HR 5.18, 95% CI = 2.45 to 10.97) were associated with increased risk of death. CONCLUSION: Screening older people for CKD may be of value, as their risk of short-term mortality, hospitalisation, and CVD is comparable with people routinely diagnosed. Larger studies with longer follow-up in more diverse and representative populations of older adults are needed to corroborate these findings.
A Review of the Ocular Phenotype and Correlation with Genotype in Poretti-Boltshauser Syndrome.
Background and Objectives: Poretti-Boltshauser syndrome (PBS) is a rare, autosomal recessive disorder caused by pathogenic variants in the LAMA1 gene, resulting in laminin dysfunction. This manifests as a cerebellar malformation with cysts, and patients present with developmental delay and ataxia; however, ocular features are not well-characterised. We aimed to summarise the ocular phenotypes of PBS based on cases reported in the literature. Materials and Methods: A literature search was conducted on Medline, Embase, and PubMed on PBS and its ocular associations. Genetically confirmed PBS cases were reviewed, and genotype-phenotype correlations were investigated. Results: Comprehensive reporting of genotypes and associated systemic and ocular phenotypes was available in 51 patients with PBS, who had 52 distinct variants in LAMA1. Most patients carried homozygous variants. The most common genotype was a c.2935delA homozygous mutation, followed by the c.768+1G>A; c.6701delC compound heterozygous mutation. High myopia was the most common ocular phenotype (n = 39), followed by strabismus (n = 27) and ocular motor apraxia (n = 26). A wide range of other ocular manifestations, including retinal dystrophy, retinal neovascularisation, retinal detachment, strabismus, nystagmus, optic disc and iris hypoplasia, were reported. Patients with the same genotype exhibited variable expressivity. Conclusions: PBS has a broad ocular phenotypic spectrum, and characterisation of this variability is important for making an accurate diagnosis and informing genetic counselling.
Perceiving temporal structure within and between the senses: A multisensory/crossmodal perspective.
The literature demonstrates that people perceive temporal structure in sequences of auditory, tactile, or visual stimuli. However, to date, much less attention has been devoted to studying the perception of temporal structure that results from the presentation of stimuli to the chemical senses and/or crossmodally. In this review, we examine the literature on the perception of temporal features in the unisensory, multisensory and crossmodal domains in an attempt to answer, among others, the following foundational questions: Is the ability to perceive the temporal structure of stimuli demonstrated beyond the spatial senses (i.e., in the chemical senses)? Is the intriguing idea of an amodal, or supramodal, temporal processor in the human brain empirically grounded? Is the perception of temporal structure in crossmodal patterns (even) possible? Does the ability to perceive temporal patterns convey any biological advantage to humans? Overall, the reviewed literature suggests that humans perceive rhythmic structures, such as beat and metre, across audition, vision and touch, exhibiting similar behavioural traits. In contrast, only a limited number of studies have demonstrated this ability in crossmodal contexts (e.g., audiotactile interactions). Similar evidence within the chemical senses remains scarce and unconvincing, posing challenges to the concept of an amodal temporal processor and raising questions about its potential biological advantages. These limitations highlight the need for further investigation. To address these gaps, we propose several directions for future research, which may provide valuable insights into the nature and mechanisms of temporal processing across sensory modalities.
Solution structure and synaptic analyses reveal determinants of bispecific T cell engager potency.
Bispecific T cell engagers (TcEs) link T cell receptors to tumor-associated antigens on cancer cells, forming cytotoxic immunological synapses (IS). Close membrane-to-membrane contact (≤13 nm) has been proposed as a key mechanism of TcE function. To investigate this and identify potential additional mechanisms, we compared four immunoglobulin G1-based (IgG1) TcE Formats (A-D) targeting CD3ε and Her2, designed to create varying intermembrane distances (A < B < C < D). Small-angle X-ray scattering (SAXS) and modeling of the conformational states of isolated TcEs and TcE-antigen complexes predicted close contacts (≤13 nm) for Formats A and B and far contacts (≥18 nm) for Formats C and D. In supported lipid bilayer (SLB) model interfaces, Formats A and B recruited, whereas Formats C and D repelled, CD2-CD58 interactions. Formats A and B also excluded bulky Quantum dots more effectively. SAXS also revealed that TcE-antigen complexes formed by Formats A and C were less flexible than complexes formed by Formats B and D. Functional data with Her2-expressing tumor cells showed cytotoxicity, surface marker expression, and cytokine release following the order A > B = C > D. In a minimal system for IS formation on SLBs, TcE performance followed the trend A = B = C > D. Addition of close contact requiring CD58 costimulation revealed phospholipase C-γ activation matching cytotoxicity with A > B = C > D. Our findings suggest that when adhesion is equivalent, TcE potency is determined by two parameters: contact distance and flexibility. Both the close/far-contact formation axis and the low/high flexibility axis significantly impact TcE potency, explaining the similar potency of Format B (close contact/high flexibility) and C (far contact/low flexibility).